How cells sculpt tissue interfaces

The National Institute of General Medical Sciences (NIGMS) at the Department of Health and Human Services awarded $420,093 to the Regents of the University of Michigan on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859). The award funds a five-year investigation into how cells self-organize to sculpt tissue interfaces and generate the characteristic curvatures that shape organ architecture and function. The research takes a systems-level approach to understand how programmed cell mechanics at epithelial-mesenchymal interfaces break symmetry during mammalian development, using the gastrointestinal tract and skin as model systems to reveal how epithelia and mesenchyme coordinately tune their mechanics to generate distinct tissue curvatures, how these curvatures are patterned across the tissue scale, and how emergent architectures are stabilized. The laboratory will integrate long-term live imaging of whole tissues at cellular resolution, biophysical and molecular mapping, functional perturbations, and computational analysis. The award is a Project Grant, with performance through May 31, 2031, at the University of Michigan in Ann Arbor, Michigan.

Abstract

Organs are built by cells, carefully organized into discrete tissue layers that must interact across shared interfaces to construct functional forms. While the genetic recipes that generate diverse cell types are well defined, we lack the corresponding blueprints for shaping the tissue architectures wherein these cells reside. The central goal of my laboratory is to uncover unifying mechanistic principles by which cells self-organize functional tissue geometries. We approach this problem from two distinct but overlapping angles: first, how local cell mechanics are programmed and propagated to drive shape and pattern during development; and second, how these processes are CO-opted to regenerate functional architecture following damage in the adult. This proposal focuses on the developmental problem, taking a systems-level approach to define how programmed cell mechanics at mammalian epithelial-mesenchymal interfaces break symmetry, transforming flat epithelial sheets into the characteristic curvatures that shape diverse organs and define their functions. The gastrointestinal tract is an ideal system to study this problem, as geometrically distinct structures such as villi of the intestine, crypts of the colon, and glands of the stomach emerge rapidly from a common symmetric template. In parallel, the mammalian skin provides a complementary model in which the dermal-epidermal interface patterns and folds into follicles with distinct geometries. By comparing these systems, we will reveal 1) how epithelia and mesenchyme coordinately tune their mechanics to generate distinct curvatures at tissue interfaces, 2) how these curvatures are patterned across the tissue scale, and 3) how emergent architectures are stabilized and reinforced. Over the next five years, my laboratory will integrate long-term live imaging of whole tissues at cellular resolution, biophysical and molecular mapping, functional perturbations, and computational modeling to establish a quantitative framework for how programmable cell behaviors are coordinated across scales to generate tissue architecture. This work will provide a foundation for understanding how form is computed by cells at tissue interfaces, with broad implications for regeneration, disease, and engineering. Because interfacial tissue folding is a universal challenge faced by nearly all organs, our findings will offer general principles of tissue shape emergence and a blueprint for preserving or rebuilding tissue architecture when IT is lost.